This program project grant revolves around the development and function of the nervous system. The two experimental organisms, Drosophila and C. elegans, underscore an additional common theme of the application: the molecular basis of neural function and behavior in genetic systems. The links between the five projects/laboratories are therefore practical as well as intellectual. In the first and second project, the Drosophila circadian clock will be investigated. There is arguably more known about the molecular basis of circadian rhythms in Drosophila than in any other eukaryotic organism. Yet there are only two identified Drosophila clock components (PER and TIM), and neural substrate features of this system are primitive. The first Project proposes to identify biochemically additional clock components, and the second Project will largely focus on neural and physiological issues that address the Drosophila pacemaker mechanism. The third Project will focus on two Drosophila genes, elav and appl. ELAV provides a vital function essential for proper formation of the nervous system, and it has recently been shown that it functions as a regulator of neuron-specific alternate splicing. The application proposes to investigate with biochemical and genetic procedures how ELAV regulates splicing, with significant input from the Rosbash laboratory. Proposed experiments on APPL will test the hypothesis that it acts as a receptor that influences neuronal arbors and synapses. The fourth Project proposes to continue and extend studies on the contribution of CaM kinase to plastic behaviors, including learning and memory. Specific aims includes the identification of neurons requiring CaM kinase, the characterization of CaM kinase- dependent biochemical pathways, and characterization of the larval neuromuscular junction phenotype of animals with alterations in these biochemical pathway. Significant input for the Hall lab on courtship conditioning as well as from White lab on tyrosine beta hydroxylase mutant is anticipated. The fifth Project proposes to study olfaction in C. elegans. Specifically, the focus is on the regulatory gene odr-7 and its role in the determination of the AWA subtype of olfactory neurons and its sensory properties. Odr-7 encodes a unique member of the nuclear receptor family of transcription factors. Specific aims include the identification and characterization of targets of odr-7 regulation, analysis of the effects of spatial and temporal control of odr-7 expression, and the identification of additional genes required for the determination of sensory specificity of the AWA neurons.